| Project/Area Number |
11470009
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Akita University |
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Principal Investigator |
INAGAKI Nobuya Akita University School of Medicine, Professor, 医学部, 教授 (30241954)
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| Co-Investigator(Kenkyū-buntansha) |
FURUKAWA Tetsushi Akita University School of Medicine, Associate Professor, 医学部, 助教授 (80251552)
YAMADA Katsuya Akita University, School of Medicine, Research Associate, 医学部, 助手 (40241666)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥8,400,000 (Direct Cost: ¥8,400,000)
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| Keywords | ATP-sensitive K^+ channel / pancreatic β -cell / insulin secretion / glucose / knockout mouse / substantia nigra / hypoxia / generalized seizures / 代謝ストレス / 神経細胞 / 高山病 / K_<ATP>チャネル / 虚血 / 静止膜電位 |
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| Research Abstract |
ATP-sensitive K^+ (K_<ATP>) channels are key molecules which link the cell's metabolic status to its membrane potential. We have determined that pancreatic β -cell K_<ATP> channel comprises the inward rectifier Kir6.2 and the sulfonylurea receptor SUR1 subunits. Our results are as follows.
# We have revealed by immunohistochmical study that SUR1 is expressed not only in pancreatic β -cells but also in glucagon-positive, somatostatin-positive, or pancreatic polypeptide-positive cells. Although the physiological role of the K_<ATP> channels in these cells is unknown, these results suggest that sulfonylureas may exert some effects on these cells through SUR1.
# We have developed the method to measure both glucose transport and its effect on the various intracellular functions in single, living pancreatic β -cells, by using a fluorescent derivative of D-glucose, 2-NBDG. By using this novel method, we have revealed that glucose metabolism as well as glucose uptake is critical in glucoseinduced insulin secretion from pancreatic β -cells, verifying the importance of K_<ATP> channels in insulin secretion.
# The substantia nigra pars reticulata (SNr), tjae area with the highest expression of K_<ATP> channels in the brain, plays a pivotal role in the control of seizures. We have shown that mutant mice lacking the Kir6.2 subunit of K_<ATP> channels (KO mice) are susceptible to generalized seizures after brief hypoxia. In normal mice, SNr neuron activity was inactivated during hypoxia by the opening of the post-synaptic K_<ATP> channels, while in KO mice the activity of these neurons was enhanced. These results suggest that K_<ATP> channels exert a depressant effect on SNr neuronal activity during hypoxia by an opening of the channels, and is involved in the nigral protection mechanism against generalized seizures.
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